Date of Award

9-21-2021

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Applied Science

First Advisor

Alexandru Biris

Second Advisor

Robert Griffin

Abstract

Exosomes are natural nanoparticles released by all eukaryotic cells studied thus far and a wide range of different biological fluids. Their components are derived from parent cells and can be transferred to other cell types and locations in an organism which makes exosome a promising nanosized-agent to treat and diagnose various diseases. Several research studies have been done to load exosomes with drugs and nucleic acids to develop a number of new therapeutic nano-vehicle. A few research studies have been done to combine these natural nanoparticles (exosomes) and artificial nanoparticles to develop a new theranostic nano-agent. In this research, we used exosomes derived from human serum, human glioblastoma exosomes, and rat primary astrocyte cells and engineered them with gold or iron oxide nanoparticles (GNPs and IONPs) using different approaches. The characterization/quantification of labeling for each approach was performed, and the comparison between these approaches investigated. Transmission electron microscopy (TEM) and photothermal microscopy (PTM) were used to visualize the labeled exosomes. The estimated number of NPs labeled per exosomes was determined based on extensive transmission electron microscopy (TEM) imaging. After successfully labeling exosomes, we studied the cellular uptake of glioblastoma exosomes and astrocyte exosomes by tumor cell or normal cell types such as stem cells and fibroblast. Our result demonstrates a proof of concept that a nanoparticle labeling system is effective for exosomal research in vitro and possible in vivo.

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